The increase in alcohol (ALC) use and abuse by adolescents during recent years poses several risks for individuals associated with growth, endocrine functions and development. Puberty-related developmental problems can occur and often vary depending upon the age that consumption and abuse begins, as well as the frequency of use, amount consumed and the duration of these habits. In females, suppressed sex steroids and delayed breast development are early indicators of developmental problems, as well as delayed or altered menarche. Similarly, research using rhesus monkeys indicated prepubertal ALC consumption caused delayed development of a regular monthly pattern of menstruation. Importantly, it has been suggested that girls using ALC have four times the chances of having delayed puberty than non-users. These examples clearly indicate the health-related significance caused by ALC use during adolescence. Studies in prepubertal rats and rhesus monkeys reveal that ALC acts at the hypothalamic level to suppress key puberty-related genes and hormones, but more research is needed to define mechanisms behind these actions. The objective of this study is to obtain information which will allow us to better understand the detrimental effects and mechanisms of action of ALC on the female pubertal process and to begin to identify potential means by which we can ameliorate some of ALCs detrimental effects. To address mechanisms, critical assessments are needed as to the actions and interactions of ALC with regard to the control of hypothalamic luteinizing hormone releasing hormone (LHRH), the peptide responsible for pubertal onset and reproductive function thereafter. Puberty is the result of the increased excitatory activation of pulsatile LHRH release, while at the same time a decrease in the prepubertal inhibitory activity occurs that has been responsible for keeping a break on the pubertal process. Using prepubertal female rats, research in this proposal will employ in vivo and in vitro techniques with molecular and physiological approaches to identify and assess upstream excitatory and inhibitory hypothalamic genes and peptides that ultimately control prepubertal LHRH secretion, discern the puberty-related substances that regulate them, and define the actions and interactions of ALC on their expressions and physiological functions. Also, specific studies will assess potential means to effectively restore development and shorten the recovery time associated with prepubertal ALC use. This research is relevant to adolescent health and development and intended to further identify the effects of ALC with regard to brain events and their actions which control female pubertal maturation. Relevance Alcohol use and abuse by adolescents poses several risks for individuals associated with growth and the timing of puberty. More basic research is needed to better understand the mechanisms by which alcohol alters the pubertal process. This proposed research is important and relevant to adolescent health and development and is intended to further identify the effects of alcohol with regard to brain events and their actions which control female pubertal maturation.